石窑当归提取物对卵巢早衰大鼠的改善作用及Rictor/mTORC2信号通路的影响

Improvement effect of Shiyao Angelica sinensis extract on premature ovarian failure rats and its effect on Rictor/mTORC2 signaling pathway

目的探讨石窑当归提取物对卵巢早衰大鼠的改善作用及Rictor/哺乳动物雷帕霉素靶蛋白复合物2(mTORC2)信号通路的影响。方法将100只Wistar雌性大鼠随机分成对照组、模型组、己烯雌酚组、石窑当归提取物低剂量组(低剂量组)、石窑当归提取物高剂量组(高剂量组),每组20只。除对照组外,其余组大鼠均采用腹腔注射环磷酰胺法建立卵巢早衰模型。建模成功后,己烯雌酚组、低剂量组、高剂量组分别给予10.0 mg/kg己烯雌酚、20.0 mg/kg及40.0 mg/kg石窑当归提取物灌胃,其他两组灌胃等体积生理盐水。4周后,采集血清测定雌二醇、卵泡生成激素(FSH)、黄体生成激素(LH)水平,观察卵巢组织病理结构,测定卵巢组织Rictor、mTORC2 mRNA和蛋白表达水平。结果病理结果显示,对照组卵巢结构正常;模型组卵泡排列松散紊乱,早期、次级、成熟卵泡明显减少;3个给药组成熟卵泡增加,可见原始卵泡和大量初级卵泡、次级卵泡,黄体较多。与对照组比较,其他组雌二醇水平以及卵巢组织Rictor、mTORC2 mRNA和蛋白表达水平降低,FSH、LH水平升高(均P<0.05);模型组、低剂量组、高剂量组、己烯雌酚组雌二醇水平以及卵巢组织Rictor、mTORC2 mRNA和蛋白水平依次升高,FSH、LH水平依次降低(均P<0.05)。结论石窑当归提取物能改善卵巢早衰大鼠性激素紊乱,并促进卵泡发育、成熟,高剂量的提取物作用更为显著,其机制可能与石窑当归提取物能激活Rictor/mTORC2信号通路有关。

Objective To investigate the improvement effect of Shiyao Angelica sinensis extract on premature ovarian failure rats and its effect on Rictor/mammalian target of rapamycin complex 2(mTORC2)signaling pathway.Methods One hundred Wistar female rats were randomly divided into control group,model group,diethylstilbestrol group,low-dose Shiyao Angelica sinensis extract group(low-dose group)and high-dose Shiyao Angelica sinensis extract group(high-dose group),with 20 rats in each group.Except the control group,a model of premature ovarian failure was established by intraperitoneal injection of cyclophosphamide in the remaining groups.After successful modeling,the diethylstilbestrol group,the low-dose group and the high-dose group were intragastrically administered diethylstilbestrol of 10.0 mg/kg,Shiyao Angelica sinensis extract of 20.0 mg/kg and 40.0 mg/kg respectively,while the other two groups were treated with isometric normal saline by gavage.After four weeks,serum levels of estradiol,follicle-stimulating hormone(FSH)and luteinizing hormone(LH)were measured,the pathological structure of ovarian tissue was observed,and the expression levels of Rictor and mTORC2 mRNAs and proteins in ovarian tissue were determined.Results The pathological results revealed that ovarian structure was normal in the control group;the arrangement of follicles was loose and disordered in the model group with significantly decreased number of early,secondary and mature follicles;mature follicles increased in the three medication groups with primordial follicles,abundant primary/secondary follicles and more corpus luteum.Compared with the control group,the other groups obtained lower estradiol level,lower expression levels of ovarian Rictor and mTORC2 mRNAs and proteins,as well as higher FSH and LH levels(all P<0.05).The estradiol level,mRNA and protein levels of ovarian Rictor and mTORC2 increased,while the levels of FSH and LH declined in the order of the model group,the low-dose group,the high-dose group and the diethylstilbestrol group(all P<0.05).Conclusion Shiyao Angelica sinensis extract,especially high-dose extract,can improve sex hormone disorder and promote follicle development and maturation in premature ovarian failure rats;its mechanism may be related to Rictor/mTORC2 signaling pathway activated by Shiyao Angelica sinensis extract.